Glutamine synthetase activity and HSP70 levels in cultured rat astrocytes: effect of 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine.
The ether lipid 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) is a membrane interactive drug selectively cytotoxic toward neoplastic cells compared to normal cells. It induces apoptosis in human leukemic HL-60, T-lymphoid and in U937 myeloid cell lines and stimulates NO biosynthesis in cultured rat astrocytes. We have found a double action of ET-18-OCH3 in astrocytes which, at low doses, promotes a moderate induction of heat shock proteins of 70 kDa (HSP70) and the increase of glutamine synthetase (GS) activity. Conversely, at high doses, the drug shows toxic effects on astrocytes inducing decrease in GS activity, low molecular weight DNA formation, and release of lactic dehydrogenase (LDH) in the culture medium. Its analog compound platelet-activating factor (PAF) shares some of these biological aspects.
Renis
M
M
Institute of Biochemistry, Faculty of Pharmacy, University of Catania, Catania, Italy. chimbio@ictuniv.unict.it
Cardile
V
V
Russo
A
A
Campisi
A
A
Collovà
F
F
D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D017124:Conserved Sequence; D053938:DNA Fragmentation; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D010742:Phospholipid Ethers / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D018840:HSP70 Heat-Shock Proteins; D009419:Nerve Tissue Proteins; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; C026659:edelfosine; D007770:L-Lactate Dehydrogenase; D005974:Glutamate-Ammonia Ligase